Diagnosis for the disease tuberculosis (TB) traditionally includes a combination of clinical, bacteriological and radiographic evidence, typically culture and smear tests, the tuberculin skin test (TST) and chest x-ray.
Antibodies specific for a number of proteins expressed by M. tuberculosis are detectable in human serum. Antibody assays are speedy and relatively inexpensive, and thus are a potentially valuable diagnostic and screening technique. There are several diagnostic categories for TB: active disease, inactive (past) TB, and two categories characterized by the absence of radiographic chest abnormality: latent infection and infection-free. Detection of active TB is, of course, clinically important. Detection of inactive TB is clinically significant, because persons with inactive TB are more than an order of magnitude more likely to develop active TB than are persons who have latent TB. Distinguishing active TB from inactive TB is significant from a public-health standpoint, as it permits concentration of resources, which are often very limited in countries most severely impacted by TB, where the danger is greatest. Distinguishing inactive TB from states characterized by normal chest x-rays is similarly important from a public-health standpoint.
Attempts to utilize detection of serum antibodies to diagnose a TB state have focused on finding an antigen or antigens whose binding correlates positively with that particular state, for example, antigens for whom positive ELISA results signal active TB. Diagnosis of TB states by antibody serum tests has suffered from lack of accuracy.
An aspect of this invention is assays for detection of human serum antibodies with improved ability to predict TB states accurately, particularly to discriminate between active TB and inactive TB.
Another aspect of this invention is reagent kits containing M. tuberculosis proteins as antigens for such antibody assays.